Compound for intraoperative molecular bioimaging, method of making the same, use thereof in intraoperative molecular bioimaging and surgical method comprising intraoperative molecular bioimaging

Abstract

The present invention provides compounds suitable for intraoperative bioimaging. In particular, compounds are provided that are suitable for marking tumor tissue during surgery to facilitate complete removal of said tumor tissue. Corresponding methods for intraoperative bioimaging and methods for surgery comprising intraoperative bioimaging are also provided.

Description

CROSS REFERENCE TO RELATED APPLICATIONS(S)[0001]This Application is a National stage filing under 35 U.S.C. 371 of International Application No. PCT / EP2019 / 052883, filed Feb. 6, 2019, which claims priority to European Application No. 18155264.7, filed Feb. 6, 2018, each of which is herein incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention provides compounds suitable for intraoperative bioimaging. In particular, compounds are provided that are suitable for marking tumor tissue during surgery to facilitate complete removal of said tumor tissue. Corresponding methods for intraoperative bioimaging and methods for surgery comprising intraoperative bioimaging are also provided.BACKGROUND OF THE INVENTION[0003]The constant development of data acquisition, storage and processing enables medical methods and therapeutic strategies to be increasingly customized for patients. As part of the pretherapeutic staging procedure, oncological relevant informa...

AI Technical Summary

Benefits of technology

The present invention provides compounds that can be used for intraoperative imaging of cancer cells. These compounds have a high affinity and selectivity for cancer cells expressing a specific receptor, and they are stable and fluoresce for a long time. The compounds can help improve surgical treatment by visualizing the location and extent of cancer tissue in real-time, allowing for better control of the cancer cells.

Problems solved by technology

The intraoperative acquisition of information on the extent and localization of invasive carcinoma tissue are limited to the clinical-visual and palpatory findings and intraoperative histological control is limited to representative areas of the soft tissue resection margins.

Loci-regional recurrences and metastases can result from potential residues of invasive carcinoma cells and represent limiting factors in curative therapy concepts.

In particular, an incomplete removal of malignant tissue reduces the success of oncological therapy concepts.

Despite the option of resection in a second surgical procedure and advances in adjuvant therapy concepts, incomplete removal of malignant tumours is often associated with higher metastasis, greater recurrence rate, higher morbidity, worse prognosis, and higher costs.

1,3 The limitations resulting from the lack of intraoperative diagnosis are particularly evident in disciplines where surgical procedures are performed in tight anatomical conditions with functionally important tissue structures.

In the case of head and neck carcinomas in particular, the incomplete removal of a malignant tumour is the greatest risk factor for dying from the disease.

4Thus, despite major advances in imaging techniques, reconstructive surgical techniques, and adjuvant therapy concepts, the lacking control over invasive carcinoma cells at the resection margin remains the major risk factor.

40b However, while the authors describe said compound to exhibit αvβ6 specific binding, there are concerns that said compound may also bind to αvβ3, so that the suitability of said compound for intraoperative bioimaging of tumor tissue of head and neck cancers, which do express αvβ6, remains questionable.

Coupling a dye to a peptide ligand involves a risk of negatively influencing binding characteristics of the ligand.

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